Process for the stereoselective preparation of insecticide 6,7,8,9,10-10-hexahalo-1, 5, 5a, 6, 9, 9a-hexadro-6, 9-methano-2, 4, 3-benzodioxathiepin-3-oxide

ABSTRACT

A process for the stereoselective preparation of insecticide 6,7,8,9,10,10-hexahalo-1,5,5a,6,9,9a-hexahydro-6,9-methano-2,4,3-benzodioxathiepin-3-oxide of the general formula 1:  
                 
 
     wherein X is a halogen such as fluorine, chlorine or bromine. The process comprises reacting 1,4,5,6,7,7-hexahalo-5-norbornene-2,3-dimethanol of the general formula IV:  
                 
 
     wherein X is as defined above, with a cyclic sulfite ring forming reagent optionally in an inert organic solvent at ambient to 139° C., wherein the reaction is carried out in the presence of a stereo isomer directing agent comprising an isomer of the compound of the formula I different from the desired isomer. The molar ratio of the stereoisomer directing agent to the dimethanol compound of the formula IV is a least 0.07.

[0001]6,7,8,9,10,10-hexahalo-1,5,5a,6,9,9a-hexahydro-6,9-methano-2,4,3-benzodioxathiepin-3-oxideare of the formula I:

[0002] wherein X may be a halogen such as fluorine, chlorine or bromine.

PRIOR ART

[0003] U.S. Pat. No. 2,799,685 describes unsaturated polycyclic sulfitesof the general formula II:

[0004] wherein X may be hydrogen or halogen or alkyl group and Y may behydrogen or alkyl group, and their derivatives containing two hydrogenatoms in 5,6-positions. These compounds are reported to exhibitinsecticidal activity. The process for the preparation of thesecompounds comprises heating a diol of the general formula III:

[0005] wherein X and Y are each as defined above, with thionyl chlorideunder heating optionally in an inert organic solvent. The product isreported to be a mixture of two isomers. The desired isomer may beresolved from the mixture, for instance by fractional crystallisationusing petroleum ether.

[0006] U.S. Pat. No. 3,251,856 describes a process for theresolution/separation of the two isomers viz α and β-isomers of6,7,8,9,10,10-hexachloro-1,5,5a,6,9,9a-hexahydro-6,9-methano-2,4,3-benzodioxathiepin-3-oxide,commonly known as endosulfan of the formula IA:

[0007] The resolution process comprises contacting the endosulfanisomeric mixture with a halogenated hydrocarbon solvent at 40-50° C.followed by cooling the mixture to 20-25° C. The resulting insolubleportion in the mixture is reported to predominantly contain the highmelting isomer viz β-isomer of endosulfan whereas the solution portionwhen subjected to evaporation results in a residue which is reported topredominantly contain the low melting isomer viz α-isomer of endosulfan.The α and β-isomers so obtained may be purified by crystallisation fromalcohol.

[0008] Both the isomers of endosulfan are reported to exhibit differentinsecticidal properties. For instance, in short exposure periods,α-endosulfan is more effective against flies than β-endosulfan. In thecase of fruit flies Drosophila melanogaster, the killing times (LT₅₀)with the use of α-endosulfan and β-endosulfan are in the ratio 1:3respectively. Insecticidal effectiveness or efficacy of α-endosulfanagainst wood boring insects is more as compared to β-endosulfan.Insecticidal effectiveness limit per m³ wood with the larvae of thehouse longhorn beetle Hylotupes bajulus L is more in the case ofβ-endosulfan as compared to α-endosulfan (Mater. Org. 1983, 18(2),81-91, Kuehne Helmut et al; CA 100 : 134245a). Both the isomers differin insecticidal persistence and biodegradability. α-Endosulfandecomposes rapidly by soil microorganisms when compared to β-endosulfan(Karachi Univ. J. Sci; 1985, 13(2), 191-7, Akhtar Shahida et al; CA 107: 91836u). α-Endosulfan is degradable by both bacteria and fungi,whereas β-endosulfan is degradable mainly by bacteria (Int. J Environ.Stud, 1981, 16 (3-4), 171-80, El Beit, I O D et al; CA 94 : 151865c).β-endosulfan has greater half life than α-endosulfan under varyingenvironmental conditions (J. Environ. Sci. Health, Part B, 1995, B30(2), 221-32, Ceron J J et al; CA 122 : 180980p). Therefore, treatmentwith β-endosulfan is particularly preferred to achieve desired efficacyover a long term.

[0009] The α and β-isomers of endosulfan are reported to be obtained inthe average isomeric ratio of about 2:1 (U.S. Pat. No. 3,251,856). Dueto the differences in the physical, chemical and biological propertiesof α and β-endosulfan and α and β-benzodioxathiepin compounds ingeneral, it is advantageous to have increased quantity of the desiredstereoisomer in the isomeric mixture depending upon the intendedspecific application of the benzodioxathiepin compound. In order toobtain required quantity of a desired isomer of the benzodioxathiepincompound, correspondingly large quantities of the substrate viz the diolcompound is required. Therefore, the above process is uneconomical.Besides, it also generates the undesired isomer in the ratio 2:1 and itsefficiency is low.

OBJECTS OF THE INVENTION

[0010] An object of the invention is to provide a process for thestereoselective preparation of6,7,8,9,10,10-hexahalo-1,5,5a,6,9,9a-hexahydro-6,9-methano-2,4,3-benzodioxathiepin-3-oxidehaving insecticidal activity, which results in increased quantity of thedesired stereoisomer in high purity without using additional quantity ofstarting material.

[0011] Another object of the invention is to provide a process for thestereoselective preparation of6,7,8,9,10,10-hexahalo-1,5,5a,6,9,9a-hexahydro-6,9-methano-2,4,3-benzodioxathiepin-3-oxidehaving insecticidal activity, which is economical.

[0012] Another object of the invention is to provide a process for thestereoselective preparation of6,7,8,9,10,10-hexahalo-1,5,5a,6,9,9a-hexahydro-6,9-methano-2,4,3-benzodioxathiepin-3-oxidehaving insecticidal activity, which is efficient.

[0013] Another object of the invention is to provide a process for thestereoselective preparation of6,7,8,9,10,10-hexahalo-1,5,5a,6,9,9a-hexahydro-6,9-methano-2,4,3-benzodioxathiepin-3-oxidehaving insecticidal activity, without using any foreign reagent whichmay introduce impurity to the product.

DESCRIPTION OF INVENTION

[0014] According to the invention there is provided a process for thestereoselective preparation of insecticide6,7,8,9,10,10-hexahalo-1,5,5a,6,9,9a-hexahydro-6,9-methano-2,43-benzodioxathiepin-3-oxide of the general formula I:

[0015] wherein X is a halogen such as fluorine, chlorine or bromine,comprising reacting 1,4,5,6,7,7-hexahalo-5-norbornene-2,3-dimethanol ofthe general formula IV:

[0016] wherein X is as defined above, with a cyclic sulfite ring formingreagent optionally in an inert organic solvent at ambient to 139° C.,wherein the reaction is carried out in the presence of a stereoisomerdirecting agent comprising an isomer of the compound of the formula Idifferent from the desired isomer, the molar ratio of the stereoisomerdirecting agent to the dimethanol compound of the formula IV being atleast 0.07.

[0017] Preferably the process comprises preparation of α-isomer of thebenzodioxathiepin-3-oxide compound in which its β-isomer is used as thestereoisomer directing agent, in the molar ratio of 0.2 to 0.8 to thedimethanol compound of the formula IV. Preferably the process comprisespreparation of β-isomer of the benzodioxathiepin-3-oxide compound inwhich its α-isomer is used as the stereoisomer directing agent, in themolar ratio of 1.7 to 4.3 to the dimethanol compound.

[0018] Preferably the process comprises preparation of α-isomer of6,7,8,9,10,10-hexachloro-1,5,5a,6,9,9a-hexahydro-6,9-methano-2,4,3-benzodioxathiepin-3-oxideie endosulfan (compound of the formula I wherein X is chlorine) in whichits β-isomer is used as the stereoisomer directing agent, the molarratio of the β-isomer of endosulfan to1,4,5,6,7,7-hexachloro-5-norbornene-2,3-dimethanol ie endosulfandiol(compound of the formula IV wherein X is chlorine) being 0.2 to 0.8.Preferably the process comprises preparation of β-isomer of6,7,8,9,10,10-hexachloro-1,5,5a,6,9,9a-hexahydro-6,9-methano-2,4,3-benzodioxathiepin-3-oxideie endosulfan (compound of the formula I wherein X is chlorine) in whichits α-isomer is used as the stereoisomer directing agent, molar ratio ofthe α-isomer of endosulfan to1,4,5,6,7,7-hexachloro-5-norbornene-2,3-dimethanol ie endosulfandiol(compound of the formula IV wherein X is chlorine) being 1.7 to 4.3.

[0019] The cyclic sulfite ring forming reagent is preferably thionylchloride.

[0020] The inert organic solvent may be aromatic hydrocarbon such astoluene or isomer of xylene such as o-xylene, m-xylene p-xylene ormixture thereof, aliphatic hydrocarbon such as n-hexane, octane,chlorinated aliphatic or aromatic hydrocarbon such as1,2-dichloroethane, 1,1,2-thichloroethane, carbontetrachloride ortrichloromethane or cyclo aliphatic hydrocarbon such as cyclohexane orany such solvent of petroleum origin. Preferably, toluene, o-xylene orcarbontetrachloride is used as the solvent. When an inert organicsolvent is not used, the reaction may be carried out in the presence ofexcess of cyclic sulfite ring forming reagent.

[0021] The stereoisomer directing agent is separated from the reactionmass in known manner, for instance by the method described in U.S. Pat.No. 3,251,856.

[0022] According to the invention practically only one of the desiredisomers viz α or β isomer is selectively prepared in high purity byusing the stereoisomer directing agent, depending upon the specificintended use thereof. For instance, to give treatments lasting a longerduration, compound of the formula I wherein X is chlorine ie endosulfan,enriched with the β-isomer is prepared; whereas for treating woodα-endosulfan enriched product is prepared. Thus the process of theinvention results in a product enriched with the desired isomer.Besides, for a given amount of the starting material the processproduces the compound of the formula 1 enriched with the desired isomerpractically devoid of the undesired isomer without consuming additionalquantities of the starting material. Therefore, the process iseconomical and efficient. Since no foreign reagent is used in thereaction and the process uses the α or β isomer of the compound of theformula I itself as the stereoisomer directing agent for the preparationof β or α isomer respectively, formation of impurities is avoided. Thestereoisomer directing agent in the product mixture is recovered andreused.

[0023] The following experimental examples are illustrative of theinvention but not limitative of the scope thereof.

[0024] Selectivity of the processes for α-endosulfan/β-endosulfan wascalculated by the equation:${Selectivity} = {\frac{\alpha \text{-}{{endosulfan}/\beta}\text{-}{endosulfan}\quad {obtained}\quad (g)}{{endosulfan}\quad {product}\quad (g)} \times 100}$

[0025] The weight of endosulfan product was computed after subtractingthe weight of SIDC-A/SIDC-B added in the reaction mixture from theweight of the product mixture.

EXAMPLE 1

[0026] Endosulfandiol (250 g, 0.693 mole), carbontetrachloride (750 ml)and β-endosulfan [stereoisomer directing agent (SIDC-A), 20 g, 0.049mole, mole ratio of SIDC-A:endosulfandiol::0.071] were heated to 65° C.with stirring. Thionyl chloride (55 ml, 0.7556 mole) was added to thereaction mixture and the reaction mixture was heated to 75° C. for 2hours. HCl generated during the reaction was scrubbed with alkalisolution. The reaction mass was cooled to 30° C. Excess thionyl chloridewas neutralised with dilute aqueous 6.5% weight/weight soda ash solutionto pH 6.5. The aqueous layer was discarded. From the organic layer,carbontetrachloride was distilled off under reduced pressure. Theproduct mixture weighing 290 g was analysed for α-endosulfan content byGas Chromatography (GC) and was found to contain 202.7 g ofα-endosulfan. SIDC-A in the product mixture was separated from theα-endosulfan as per the procedure of U.S. Pat. No. 3,251,856 and reused.The selectivity of the process for α-endosulfan was found to be 75.07%.

EXAMPLES 2 to 12

[0027] The procedure of Example 1 was followed using differentquantities of SIDC-A and the results were as in the following Table 1:TABLE 1 SIDC-A: Endosulfandiol Endosulfan Selectivity Eg EndosulfandiolSIDC-A mole product α-Endosulfan for α- No (mol) (mol) ratio (g) (g)endosulfan 2 0.693 0 0 273 190.6 69.81 3 0.693 0.098 0.141 275 220.880.3 4 0.693 0.147 0.212 271 235.7 86.97 5 0.693 0.197 0.284 271 245.790.66 6 0.693 0.246 0.355 271 264.2 97.49 7 0.693 0.295 0.426 277 277.1100.0 8 0.693 0.344 0.496 269 266.7 99.14 9 0.693 0.399 0.576 272 267.898.46 10 0.693 0.442 0.638 272 266.7 98.05 11 0.693 0.491 0.709 273264.4 96.85 12 0.693 0.540 0.779 274 271.2 98.98

EXAMPLES 13 to 24

[0028] The procedure of Examples 1 to 12 were followed using o-xylene asthe solvent and the results were as in the following Table 2: TABLE 2SIDC-A: Endosulfandiol Endosulfan Selectivity Eg Endosulfandiol SIDC-Amole product α-Endosulfan for α-endosulfan No (mol) (mol) ratio (g) (g)(%) 13 0.693 0 0 273 179.00 65.57 14 0.693 0.049 0.071 273 191.33 70.0815 0.693 0.098 0.141 273 204.86 75.04 16 0.693 0.147 0.212 273 217.4579.65 17 0.693 0.197 0.284 273 230.69 84.50 18 0.693 0.246 0.355 273243.94 89.36 19 0.693 0.295 0.426 273 256.0 93.77 20 0.693 0.344 0.496273 270.02 98.91 21 0.693 0.399 0.576 273 269.76 98.81 22 0.693 0.4420.638 272 269.17 98.96 23 0.693 0.491 0.709 273 270.79 99.19 24 0.6930.540 0.779 276 271.41 98.34

EXAMPLES 25 to 36

[0029] The procedure of Examples 1 to 12 were followed using toluene asthe solvent and the results were as in the following Table 3: TABLE 3SIDC-A: Endosulfandiol Endosulfan Selectivity Eg Endosulfandiol SIDC-Amole product α-Endosulfan for α-endosulfan No (mol) (mol) ratio (g) (g)(%) 25 0.693 0 0 273 175.8 64.4 26 0.693 0.049 0.071 273 188.4 69.0 270.693 0.098 0.141 273 201.9 74.0 28 0.693 0.147 0.212 273 213.8 78.3 290.693 0.197 0.284 273 227.3 83.3 30 0.693 0.246 0.355 273 241.0 88.3 310.693 0.295 0.426 273 252.3 92.4 32 0.693 0.344 0.496 273 265.6 97.3 330.693 0.399 0.576 273 269.8 98.8 34 0.693 0.442 0.638 273 265.2 97.2 350.693 0.491 0.709 273 270.8 99.2 36 0.693 0.540 0.779 273 269.8 98.8

EXAMPLES 37 to 41

[0030] The procedure of example 8 was followed varying the temperaturesand the results were as shown in the following Table 4. TABLE 4 ExampleNo 37 38 39 40 41 Endosulfandiol 0.693 0.693 0.693 0.693 0.693 (mole)SIDC-A 0.344 0.344 0.344 0.344 0.344 (mole) SIDC-A to 0.497 0.497 0.4970.497 0.497 Endosulfandiol mole ratio Reaction temperature 15 25 35 5075 (° C.) Reaction time (hrs) 8 6 4 2 1 Endosulfan product 269 268 270269 266 (gms) α-Endosulfan content 266.6 265.2 266.9 266.6 265.5 in theproduct mixture (gms) Selectivity for α- 99.10 98.95 98.85 99.10 99.81Endosulfan (%)

EXAMPLE 42

[0031] Endosulfandiol (250 g. 0.69 mole), carbontetrachloride (750 ml)and α-endosulfan [stereoisomer directing agent (SIDC-B), 100 g, 0.25mole, SIDC-B:endosulfandiol::0.355] were heated to 65° C. with stirring.Thionyl chloride (55 ml, 0.7556 mole) was added to the reaction mixtureand the reaction mixture was heated to 75° C. for 2 hours. HCl generatedduring the reaction was scrubbed with alkali solution. The reaction masswas cooled to 30° C. Excess thionyl chloride was neutralised with diluteaqueous 6.5°/weight/weight soda ash solution to pH 6.5. The aqueouslayer was discarded. From the organic layer, carbontetrachloride wasdistilled off under reduced pressure. The product mixture weighing 374 gwas analysed for β-endosulfan content by Gas Chromatogrphy (GC) and wasfound to contain 106.9 g of β-endosulfan. SIDC-B in the product mixturewas separated from the β-endosulfan as per the procedure of U.S. Pat. No3,251,856 and reused. The selectivity of the process for β-endosulfanwas found to be 39.01%.

EXAMPLES 43 to 53

[0032] The procedure of Example 42 was followed with varying quantitiesof SIDC-B and the results were as in the following Table 5: TABLE 5SIDC-B: endosulfandiol Endosulfan Selectivity Eg Endosulfandiol SIDC-Bmole product β-Endosulfan for β-endosulfan No (mol) (mol) ratio (g) (g)(%) 43 0.693 0 0 273 77.8 28.5 44 0.693 0.49 0.709 274 135.3 49.37 450.693 0.74 1.064 274 163.9 59.82 46 0.693 0.98 1.418 275 193.0 70.18 470.693 1.23 1.773 273 220.8 80.90 48 0.693 1.47 2.127 273 249.3 91.32 490.693 1.72 2.482 275 272.0 98.91 50 0.693 1.97 2.836 274 273.7 99.89 510.693 2.21 3.191 274 272.7 99.53 52 0.693 2.46 3.545 275 274.0 99.64 530.693 2.95 4.255 274 273.7 99.89

EXAMPLES 54 to 65

[0033] The procedure of Examples 42 to 53 were followed using o-xyleneas the solvent and the results were as in the following Table 6: TABLE 6SIDC-B: Endosulfandiol Endosulfan Selectivity Eg Endosulfandiol SIDC-Bmole product β-Endosulfan for β-endosulfan No (mol) (mol) ratio (g) (g)(%) 54 0.693 0 0 274 88.2 32.19 55 0.693 0.25 0.355 273 121.3 44.43 560.693 0.49 0.709 274 155.0 56.57 57 0.693 0.74 1.064 274 188.4 68.75 580.693 0.98 1.418 274 221.8 80.93 59 0.693 1.23 1.773 275 255.5 92.90 600.693 1.47 2.217 273 271.7 99.52 61 0.693 1.72 2.482 273 272.4 99.78 620.693 1.97 2.836 275 274.0 99.64 63 0.693 2.21 3.191 276 273.2 99.00 640.693 2.46 3.545 275 274.0 99.64 65 0.693 2.95 4.255 274 272.4 99.42

EXAMPLES 66 to 77

[0034] The procedure of Examples 42 to 53 were followed using toluene asthe solvent and the results were as in the following Table 7: TABLE 7SIDC-B: Endosulfandiol Endosulfan Selectivity Eg Endosulfandiol SIDC-Bmole product β-Endosulfan for β-endosulfan No (mol) (mol) ratio (g) (g)(%) 66 0.693 0 0 273 84.6 31.00 67 0.693 0.25 0.355 274 117.3 42.81 680.693 0.49 0.709 274 149.6 54.59 69 0.693 0.74 1.064 274 181.9 66.38 700.693 0.98 1.418 275 214.9 78.15 71 0.693 1.23 1.773 273 246.2 90.18 720.693 1.47 2.217 273 271.7 99.52 73 0.693 1.72 2.482 275 273.0 99.27 740.693 1.97 2.836 274 273.7 99.91 75 0.693 2.21 3.191 274 272.8 99.55 760.693 2.46 3.545 275 274.0 99.64 77 0.693 2.95 4.255 274 273.8 99.93

EXAMPLES 78-82

[0035] The procedure of example 61 was followed varying the temperatureand the results were as shown in the following Table 8. TABLE 8 ExampleNo 78 79 80 81 82 Endosulfandiol 0.693 0.693 0.693 0.693 0.693 (mole)SIDC-B 1.72 1.72 1.72 1.72 1.72 (mole) SIDC-B:Endosulfandiol 2.482 2.4822.482 2.482 2.482 mole ratio Reaction temperature 15 25 35 50 75 (° C.)Reaction time (hrs) 8 6 4 2 1 Endosulfan product 274 272.9 273.2 274 273(gms) 62 -Endosulfan 270.9 270.0 271.0 270.8 267.5 content in theproduct mixture (gms) Selectivity for 98.89 98.94 99.19 98.83 97.98β-Endosulfan (%)

[0036] The results of Examples 1 to 36 as shown in Tables 1 to 3 clearlyshow that selectivity of the process for α-endosulfan depends on themolar ratio of SIDC-A to endosulfandiol. Similarly the results ofExamples 42 to 77 as shown in Tables 5 to 7 clearly show thatselectivity of the process for β-endosulfan depends on the molar ratioof SIDC-B to endosulfandiol. The results of Examples 37 to 41 and 78 to82 as shown in Tables 4 and 8 clearly indicate that temperature haspractically no effect on the selectivity of the process for α-endosulfanor β-endosulfan.

1) A process for the stereoselective preparation of insecticide6,7,8,9,10,10-hexahalo-1,5,5a,6,9,9a-hexahydro-6,9-methano-2,4,3-benzodioxathiepin-3-oxideof the general formula 1:

wherein X is a halogen such as fluorine, chlorine or bromine, comprisingreacting 1,4,5,6,7,7-hexahalo-5-norbornene-2,3-dimethanol of the generalformula IV:

wherein X is as defined above, with a cyclic sulfite ring formingreagent optionally in an inert organic solvent at ambient to 139° C.,wherein the reaction is carried out in the presence of a stereo isomerdirecting agent comprising an isomer of the compound of the formula Idifferent from the desired isomer, the molar ratio of the stereoisomerdirecting agent to the dimethanol compound of the formula IV being atleast 0.07. 2) A process as claimed in claim 1 for the preparation ofα-isomer of the benzodioxathiepin-3-oxide compound in which its β-isomeris used as the stereo isomer directing agent in the molar ratio of 0.2to 0.8 to the dimethanol compound. 3) A process as claimed in claim 1for the preparation of β-isomer of the benzodioxathiepin-3-oxidecompound in which its α-isomer is used as the stereo isomer directingagent in the molar ratio of 1.7 to 4.3 to the dimethanol compound. 4) Aprocess as claimed in claim 1 for the preparation of α-isomer of6,7,8,9,10,10-hexachloro-1,5,5a,6,9,9a-hexahydro-6,9-methano-2,4,3-benzodioxathiepin-3-oxideie endosulfan (compound of the formula I wherein X is chlorine) in whichits β-isomer is used as the stereoisomer directing agent, the molarratio of the β-isomer of endosulfan to1,4,5,6,7,7-hexachloro-5-norbornene-2,3-dimethanol ie endosulfandiol(compound of the formula IV wherein X is chlorine) being 0.2 to 0.8. 5)A process as claimed in claim 1 for the preparation of β-isomer of6,7,8,9,10,10-hexachloro-1,5,5a,6,9,9a-hexahydro-6,9-methano-2,4,3benzodioxathiepin-3-oxideie endosulfan (compound of the formula I wherein X is chlorine) in whichits α-isomer is used as the stereoisomer directing agent, molar ratio ofthe α-isomer of endosulfan to1,4,5,6,7,7-hexachloro-5norbornene-2,3-dimethanol ie endosulfandiol(compound of the formula IV wherein X is chlorine) being 1.7 to 4.3. 6)A process as claimed in claim 1, wherein the cyclic sulfite ring formingreagent is thionyl chloride. 7) A process for the stereoselectivepreparation of insecticide6,7,8,9,10,10-hexahalo-1,5,5a,6,9,9a-hexahydro-6,9-methano-2,4,3-benzodioxathiepin-3-oxideof the general formula 1:

wherein X is a halogen such as fluorine, chlorine or bromine,substantially as herein described particularly with reference toExamples 1, 3 to 12, 14 to 24, 26 to 42, 44 to 53, 55 to 65 and 67 to 82herein.